Drug Trials Snapshots: CARDAMYST
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the CARDAMYST Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
CARDAMYST (etripamil) nasal spray
(kar-da-mist)
Milestone Pharmaceuticals, Inc.
Approval date: December 12, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
CARDAMYST is a calcium channel blocker indicated for the rapid conversion of acute paroxysmal supraventricular tachycardia (PSVT) episodes to sinus rhythm in adults. PSVT is a type of abnormally fast heart rhythm that starts suddenly and can cause symptoms like palpitations, dizziness, chest discomfort, and shortness of breath.
How is this drug used?
CARDAMYST is a nasal spray that patients self-administer at home when experiencing PSVT symptoms. The dose is 70 mg (one spray in each nostril). If symptoms persist after 10 minutes, a second 70 mg dose may be taken.
Who participated in the clinical trials?
The FDA approved CARDAMYST based on evidence from a clinical trial of 255 patients with symptoms of perceived PSVT. The trial was conducted at 160 sites in eight countries in Belgium, Canada, Germany, Spain, Hungary, Netherlands, Poland, and the United States. The trial enrolled 74 patients from the United States and 181 patients from outside the United States. Safety of CARDAMYST was evaluated using all clinical trials in patients with PSVT. Therefore, the number of patients representing efficacy findings may differ from the number of patients representing safety findings due to different pools of study participants analyzed for efficacy and safety.
How were the trials designed?
CARDAMYST was evaluated in the RAPID study (NCT03464019), a randomized, double-blind, placebo-controlled, multicenter, event-driven study in 255 patients with an episode of PSVT and self-administered the study drug. The effect of CARDAMYST was evaluated by time-to-conversion of confirmed PSVT to normal heart rhythm (sinus rhythm, SR) for at least 30 seconds within 30 minutes after the administration of CARDAMYST.
How were the trials designed?
CARDAMYST was evaluated in the RAPID study (NCT03464019), a randomized, double-blind, placebo-controlled, multicenter, event-driven study. The population for this study was adult patients at least 18 years of age who had an electrocardiographically documented history of PSVT and history of sustained episodes of PSVT (i.e., typically lasting approximately 20 minutes or longer).
Patients were randomized in a 1:1 ratio to a dosing regimen in which a repeat dose of study drug (i.e., 2×70 mg of etripamil or 2× placebo) could be administered if perceived PSVT symptoms persisted at 10 minutes after the first dose in a medically unsupervised setting.
The primary endpoint was time to an adjudicated termination of a confirmed episode of PSVT and conversion to sinus rhythm for at least 30 seconds within 30 minutes of start of study drug. Both the baseline demographics and the efficacy information shown below are based on the patient population who self-administered CARDAMYST for a perceived episode of PSVT. This population is termed modified intent-to-treat (mITT) population.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of CARDAMYST.
Figure 1. Baseline Demographics by Sex, mITT Population
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the efficacy of CARDAMYST.
Figure 2. Baseline Demographics by Race, mITT Population
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial used to evaluate the efficacy of CARDAMYST.
Figure 3. Baseline Demographics by Age, mITT Population
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of patients by ethnicity enrolled in the clinical trial used to evaluate the efficacy of CARDAMYST.
Figure 4. Baseline Demographics by Ethnicity, mITT Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, RAPID Trial, mITT Population
| Demographic | CARDAMYST N=135 | Placebo N=120 | Total N=255 |
|---|---|---|---|
| Age, years | |||
| Mean (SD) | 52.4 (13.96) | 56.2 (12.00) | 54.2 (13.19) |
| Age group, years, n (%) | |||
| <70 | 119 (88.1) | 103 (85.8) | 222 (87.1) |
| ≥70 | 16 (11.9) | 17 (14.2) | 33 (12.9) |
| Sex, n (%) | |||
| Female | 93 (68.9) | 88 (73.3) | 181 (71.0) |
| Male | 42 (31.1) | 32 (26.7) | 74 (29.0) |
| Race, n (%) | |||
| American Indian or Alaska Native | 1 (<1) | 0 | 1 (<1) |
| Asian | 2 (1.5) | 4 (3.3) | 6 (2.4) |
| Black or African American | 4 (3.0) | 3 (2.5) | 7 (2.7) |
| Other | 2 (1.5) | 3 (2.5) | 5 (2.0) |
| White | 126 (93.3) | 110 (91.7) | 236 (92.5) |
| Ethnicity, n (%) | |||
| Hispanic or Latino | 7 (5.2) | 9 (7.5) | 16 (6.3) |
| Not Hispanic or Latino | 126 (93.3) | 109 (90.8) | 235 (92.2) |
| Unknown | 2 (<1) | 2 (<1) | 4 (<1) |
Source: Adapted from FDA Review
Abbreviation: mITT, modified intent-to-treat; SD, standard deviation
What are the benefits of this drug?
CARDAMYST helps restore your normal heartbeat when you experience a specific type of irregular heart rhythm problem.
What are the benefits of this drug (results of trials used to assess efficacy)?
In RAPID trial, the primary efficacy endpoint of time to conversion of PSVT to SR within 30 minutes was greater with CARDAMYST compared to placebo as shown in Table 2.
Table 2. Time to Conversion of PSVT to SR Within 30 Minutes, RAPID Trial, mITT Population
| Category | CARDAMYST N=135 | Placebo N=120 |
|---|---|---|
| Kaplan-Meier estimate for subjects converted to SR within 30 minutes, %a | 49.6 | 22.7 |
| Treatment comparisons | ||
| Hazard ratio (95% CI)b | 2.59 (1.64, 4.09) | |
| p-valuec | <0.001 | |
Source: Adapted from FDA Review
a Subjects converting after additional medication interventions are censored after the end of the observation period.
b The hazard ratio and 95% confidence interval are calculated using the Cox proportional hazards model.
c p-value is obtained from the Wilcoxon test.
Abbreviations: CI, confidence interval; mITT, modified intent-to-treat; N, number of subjects; PSVT, paroxysmal supraventricular tachycardia; SR, sinus rhythm
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: CARDAMYST worked similarly in males and females.
- Race: The number of patients of races other than White is small; therefore, difference in treatment effect between races could not be determined.
- Age: CARDAMYST worked similarly across age groups.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Analysis of Time to Conversion of PSVT to SR Within 30 Minutes by Subgroup, mITT Population
| Demographic | Subgroup | Hazard Ratio (95% CI) |
|---|---|---|
| Sex | Female | 2.5 (1.5, 4.1) |
| Male | 2.8 (1.4, 5.5) | |
| Age, years | <70 | 2.6 (1.6, 4.2) |
| ≥70 | 2.3 (0.9, 5.4) |
Source: Adapted from FDA Review
Note: Treatment differences and credible intervals include the relevance of outcomes from other subgroups.
Abbreviations: CI, credible intervals; mITT, modified intent-to-treat; PSVT, paroxysmal supraventricular tachycardia; SR, sinus rhythm
What are the possible side effects?
CARDAMYST may cause serious side effect, including fainting due to CARDAMYST effects on blood pressure, heart rate, and electrical activity of the heart. CARDMYST may cause dizziness and fainting, especially in people with a history of fainting and certain heart problems, or people with a history of fainting during an episode of PVST.
The most common side effects of CARDAMYST are nasal discomfort, nasal congestion, runny nose, throat irritation, and nosebleed.
What are the possible side effects (results of trials used to assess safety)?
The majority of treatment-related adverse reactions reported in clinical studies with CARDAMYST have been related to local reactions to, at, or near the nasal administration site, including the nose, throat, and eyes. These local reactions included nasal discomfort, nasal congestion, throat irritation, oropharyngeal pain, lacrimation, rhinorrhea, bleeding from the nose, upper-airway cough syndrome, and sneezing.
Table 3. Most Frequent (≥5.0%) Adverse Reactions1 Observed in Randomized Controlled Studies, Safety Population
| Adverse Reaction | CARDAMYST N=321 n (%) | Placebo N=223 n (%) |
|---|---|---|
| Nasal discomfort | 86 (27) | 14 (6) |
| Nasal congestion | 43 (14) | 3 (1) |
| Rhinorrhoea | 37 (11) | 4 (2) |
| Throat irritation | 22 (7) | 3 (1) |
| Epistaxis | 20 (6) | 3 (1) |
Source: Adapted from FDA Review
1.Adverse reactions that occurred within 24 hours of study drug administration for perceived PSVT in the pooled double-blind, placebo-controlled studies that had an overall incidence of 5% or greater and where the incidence is at least 1% greater than the placebo group.
Abbreviations: PSVT, paroxysmal supraventricular tachycardia
Because of effects on blood pressure, heart rate, and cardiac conduction, CARDAMYST may cause dizziness and/or syncope, especially in patients with a history of syncope and high-grade atrioventricular (AV) block or sinus node dysfunction, or those with a history of syncope during an episode of PSVT.
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in side effects between race could not be determined. However, the occurrence of side effects was similar between White and Black or African American participants.
- Age: The occurrence of side effects was similar in patients younger and older than 70 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 4. Side Effects by Sex, Race, and Age, Safety Population
| Parameter | CARDAMYST N=321 n/Ns (%) | Placebo N=223 n/Ns (%) |
|---|---|---|
| Nasal reactions1 | 126/321 (39) | 21/223 (9) |
| Sex | ||
| Female | 89/213 (42) | 14/149 (9) |
| Male | 37/108(34) | 7/74 (10) |
| Race | ||
| White | 112/287(39) | 20/200(10) |
| Black or African American | 6/14 (43) | 1/9 (11) |
| Other | 8/20 (40) | 0/14 (0) |
| Age, years | ||
| <70 | 111/275 (40) | 19/194 (10) |
| ≥70 | 15/46(33) | 2/29 (7) |
Source: Adapted from FDA Review
1 Nasal reactions include side effects of nasal discomfort, nasal congestion, rhinorrhea, or epistaxis
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.